Therapeutic potential of chrysin in regulation of interleukin-17 signaling in a repeated intranasal amyloid-beta-induced Alzheimer's disease model

: The aim of the current study was to study the therapeutic potential of chrysin against repeated intranasal amyloid-beta (Aβ)-induced interleukin-17 (IL-17) signaling in a mouse model of AD. : Male BALB/c mice were daily exposed to intranasal Aβ (10 μg/10 μL) for seven consecutive days. Chrysin was orally administered at doses of 25, 50 and 100 mg kg in 0.5% sodium carboxy methyl cellulose suspension from day 5 of Aβ administration for seven days. Following the treatment, the memory of the animals was appraised using Morris water maze, novel object recognition and passive avoidance tests. Further, the effects of chrysin on Aβ -induced IL-17 signaling and redox levels were evaluated in the cortex and hippocampus regions of the mouse brain through western blot and immunohistochemistry. : The exposure to Aβ through the intranasal route induced a significant decline in the spatial, learning and cognitive memory of the animals, and most interestingly, exposure to Aβ triggered IL-17-mediated signaling, which resulted in a significant increase in the expression of IL-17RA, Act1 and TRAF6. Furthermore, Aβ impaired the tissue redox level and inflammatory cytokines in the mouse brain. Alternatively, treatment with chrysin at 25, 50 and 100 mg kg oral doses alleviated Aβ -mediated memory decline, impaired redox levels and inflammation. Specifically, chrysin downregulated the expression of IL-17 and mediated signaling in the brain regions of the mice. : Chrysin was evidenced to be a potent antioxidant and anti-inflammatory agent, clearly showing a protective role against Aβ -induced IL-17-mediated inflammation in the brain of the mice.